Ex Parte Ueda et al

Patent Trials and Appeals Board

Mar 13, 2019

14381366 - (D) (P.T.A.B. Mar. 13, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/381,366 08/27/2014
35811 7590 03/15/2019
IP GROUP OF DLA PIPER LLP (US)
ONE LIBERTY PLACE
1650 MARKET ST, SUITE 4900
PHILADELPHIA, PA 19103
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
Yoji Ueda
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
TAN-14-1394 2229
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
03/15/2019 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
pto. phil@dlapiper.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YOJI UEDA and FUMIO NAKAMURA
Appeal2018-005971
Application 14/381,366
Technology Center 1600
Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134(a) involving claims to a
process for detecting a target nucleic acid. The Examiner rejected the claims
as including improper dependent claims, omitting essential subject matter,
failing to comply with the enablement and written description requirements,
and being directed to patent-ineligible subject matter. 3 We have jurisdiction
1 The real party in interest is identified as Toray Industries, Inc. (see Br. 1 ).
2 We have considered and herein refer to the Specification of Aug. 27, 2014
("Spec."); Final Office Action of Mar. 23, 2017 ("Final Act."); Appeal Brief
of Sept. 6, 2017 ("Br."); and Examiner's Answer of Feb. 6, 2018 ("Ans.").
3 The Examiner withdrew the rejection of claims 1-3, 5, 7-13, and 16-20
under 35 U.S.C. § 101 for lacking utility (Ans. 36).
Appeal2018-005971
Application 14/381,366
under 35 U.S.C. § 6(b). We affirm-in-part and enter a new ground of
rejection.
Statement of the Case
Background
"In sandwich hybridization, detection is generally carried out after
preliminarily amplifying the sample by a nucleic acid amplification
technique such as PCR" (Spec. ,r 4). However, using PCR may amplify
contaminated DNA and requires increasing the number of primers to
simultaneously detect a plurality of genes (see id.). Detection methods
without PCR amplification include sensitization techniques that "require a
special enzyme or complex reaction, or special support ... or special
luminous body" (id. ,r 5). Without using nucleic acid amplification or a
sensitization technique, "the present inventors discovered that, in sandwich
hybridization, a target nucleic acid can be detected with high sensitivity by
simultaneously hybridizing a plurality of detection probes that hybridize
with different regions in the target nucleic acid" (id. ,r 7).
The Claims
Claims 1-3, 5, 7-13, and 16-20 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A method of improving sensitivity of detection of a
presence or absence of a target nucleic acid comprising:
sequentially or simultaneously bringing
a fragmentation product of a target nucleic
acid,
a plurality of detection probes that are
complementary to different regions of the target
nucleic acid, and
2
Appeal2018-005971
Application 14/381,366
a capture probe that is complementary to a
region of the target nucleic acid and is
immobilized on a support,
into contact with each other under
hybridizing conditions to hybridize said capture
probe with said fragmentation product of said
target nucleic acid and to hybridize said
fragmentation product with said plurality of
detection probes,
thereby binding said plurality of detection
probes to said support through said capture probe
and said fragmentation product of said target
nucleic acid; and
detecting the presence or absence of said plurality of
detection probes bound to said support,
wherein a mode of the nucleic acid length of said target
nucleic acid or fragmentation product thereof to be hybridized
with said capture probe is 100 bases to 1500 bases.
The Issues
A. The Examiner rejected claim 18 under 35 U.S.C. § 112 (pre-AIA),
fourth paragraph as being an improper dependent claim (Final Act.
3--4).
B. The Examiner rejected claims 1-3, 5, 7-13, and 16-20 under
35 U.S.C. § 112, second paragraph, for omitting essential subject
matter (Final Act. 4). 4
4 The Examiner cites to 35 U.S.C. § 112, second paragraph for this rejection,
however, failure to recite essential subject matter in the claims is a rejection
under 35 U.S.C. § 112, first paragraph. See In re Mayhew, 527 F.2d 1229,
1232 (CCPA 1976).
3
Appeal2018-005971
Application 14/381,366
C. The Examiner rejected claims 1-3, 5, 7-13, and 16-20 under
35 U.S.C. § 112, first paragraph as failing to comply with the
enablement requirement (id. at 5-19).
D. The Examiner rejected claims 1-3, 5, 7-13, and 16-20 under
35 U.S.C. § 112, first paragraph as failing to comply with the
written description requirement (id. at 19-30).
E. The Examiner rejected claims 1, 2, and 7 under 35 U.S.C. § 101, as
being directed to patent-ineligible subject matter (id. at 37--49).
A. 35 US.C. § 112,fourth paragraph
The Examiner finds claim 18 is an improper dependent claim for
depending from cancelled claim 4 (Final Act. 3--4). Appellants failed to
contest the improper dependent claim rejection appeal.
When the appellant fails to contest a ground of rejection to the
Board[,] ... the Board may treat any argument with respect to
that ground of rejection as waived. In the event of such a
waiver, the PTO may affirm the rejection of the group of claims
that the examiner rejected on that ground without considering
the merits of those rejections.
Hyattv. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008).
In the absence of Appellants' argument on the improper dependent
claim, we consider the argument waived and summarily affirm the
Examiner's rejection. See 37 C.F.R. § 4I.37(c)(l)(iv) ("[A]ny arguments or
authorities not included in the appeal brief will be refused consideration by
the Board for purposes of the present appeal.").
4
Appeal2018-005971
Application 14/381,366
B. 35 USC§ 112,first paragraph (omitting essential matter)
The Examiner finds claim 1 is "incomplete for omitting essential
steps, such omission amounting to a gap between the steps" (Final Act. 4 ).
The Examiner finds that "[t]he omitted steps are: a) the generation of
fragmentation products of a target nucleic acid; b) the determination of the
size of the fragments of the target nucleic acid; and c) the determination of
the mode of the length of the target nucleic acid" (id.).
We find the Examiner erred. As Appellants correctly point out "the
language 'bringing a fragmentation product of a target nucleic acid ... into
contact with [ a capture probe and detection probes]' fundamentally implies
that the fragmentation product has been generated, either by fragmentation
methods or by natural means" (Br. 3--4 ). Likewise, "one skilled in the art
would reasonably understand that the steps of affirmatively determining the
size of the fragments and mode of the length of the target nucleic acid are
not necessary to detect the presence or absence of the target nucleic acid"
(id. at 4). Because we do not find any missing elements or steps, we reverse
the Examiner's erroneous rejection under 35 U.S.C. § 112, first paragraph
for omitting essential subject matter.
C 35 USC§ 112, scope of enablement
The Examiner finds
that the claimed method does not require the use of any
detectable label. Further, the amended method does not require
the removal of detection probes that are bound non-specifically
to the solid support prior to performing the detection of said
detection probe. It is further noted that the claimed method
does not require that the probes bind with any degree of
5
Appeal2018-005971
Application 14/381,366
specificity for the target, nor exclude the non-specific
hybridization of probes to non-target sequences
(Final Act. 7). The Examiner finds:
In order to practice the full scope of the invention, one would
have to determine the nucleotide sequence for each and every
organism, much less any gene of interest, in order to identify
the correct nucleotide sequences for all target sequences as well
as the detection probes and capture probes that are essential to
the claimed invention
(id. at 13). The Examiner determines "[i]n view of the breadth of scope
claimed, the limited guidance provided, the unpredictable nature of the art to
which the claimed invention is directed, and in the absence of convincing
evidence to the contrary, the claims are deemed to be non-enabled by the
disclosure" (id. at 17).
We find the Examiner erred. As Appellants correctly point out:
Applying the Wands factors, the state of the art of molecular
biology and the detection of nucleic acids is quite developed,
the skill in the art associated with molecular biology and the
detection of nucleic acid sequences is quite high (i.e., generally
Ph.D. level), and the [S]pecification has a number of working
examples (e.g., Examples 1 and 2 showing the claimed method
in detecting human papilloma virus and Example 3 showing
detection of SNPs)
(Br. 5).
Some experimentation, even a considerable amount, is not "undue" if,
e.g., it is merely routine, or if the Specification provides a reasonable
amount of guidance as to the direction in which the experimentation should
proceed. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
There can be no reasonable dispute that a person of ordinary skill in
the art would be able to detect a target, i.e. known, nucleic acid, by using a
6
Appeal2018-005971
Application 14/381,366
known sandwich hybridization procedure (see Spec. ,r 3) with known
capture probes (see id. ,r 32) and detection probes (see id. ,r 39), wherein a
mode of the nucleic acid length of said target nucleic acid or fragmentation
product thereof (see id. ,r,r 24--25) to be hybridized with said capture probe is
100 bases to 1500 bases (see id. ,r,r 26, 28), following the disclosure of
Appellants' Specification.
Therefore, in light of the absence of undue experimentation in
performing the method of improving the sensitivity of detection of a nucleic
acid, we reverse the Examiner's erroneous enablement rejection.
D. 35 US.C. § 112, written description
The Examiner finds "the claimed method fairly encompasses the
detection of the millions of bacteria thought to exist as well as the 5676
species of mammals and 32,000 species of fish known to exist, yet not one
sequence from any of these animals has been disclosed" (Final Act. 30).
The Examiner finds
[ w ]hile claim 1 now requires that "a mode of the nucleic acid
length of said target nucleic acid or fragmentation product
thereof to be hybridized with said capture probe is 100 bases to
1500 bases," no sequence that is 100 bases, much less 1500
bases in length has been disclosed
(id. at 26). The Examiner finds that "[t]he aspect that the claims recite the
limitation 'target nucleic acid' ( claim 1 ), or that it is 'an animal-derived
sample' ( claim 8) or even that it is from a human ( claim 10) is not
considered to satisfy the written description for same" (id. at 28).
We find that the Examiner erred. As Appellants correctly point out,
"the claims are directed to methods of detecting target sequences using novel
methods-not nucleic acid sequences per se" (Br. 4). See Palko-Gunter
7
Appeal2018-005971
Application 14/381,366
Falkner v. Inglis, 448 F.3d 1357, 1368 (Fed. Cir. 2006) ("[A] requirement
that patentees recite known DNA structures, if one existed, would serve no
goal of the written description requirement.").
[T]he determination of what is needed to support generic claims
to biological subject matter depends on a variety of factors,
such as the existing knowledge in the particular field, the extent
and content of the prior art, the maturity of the science or
technology, the predictability of the aspect at issue, and other
considerations appropriate to the subject matter.
Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005).
There can be no reasonable dispute that the method would function
with any known target nucleic acid which is subject to fragmentation by
known processes (see Spec. ,r,r 24--28) or naturally occurs within the desired
length, and is subject to hybridization with appropriately homologous
capture and detection probes (see id. ,r,r 31--44).
Therefore, in light of the absence of any unpredictability in
performing the generic claim to a method of improving the sensitivity of
detection of a nucleic acid, we reverse the Examiner's erroneous written
description rejection.
E. 35 USC§ 101, patent eligible subject matter
The Examiner rejected claims 1, 2, and 7 under 35 U.S.C. § 101 as
being directed to patent-ineligible subject matter (Final Act. 40). In
particular, the Examiner finds that the claims "are directed to a combination
of natural phenomena- nucleic acids and [their] ability to hybridize to
complementary sequences; and a natural relationship- the more detectable
probes that bind to a given sequence, the better one is able to detect same
(increase sensitivity)" (id. at 42).
8
Appeal2018-005971
Application 14/381,366
To determine whether a claim is patent eligible under§ 101, we
employ the two-step Alice framework. In step one, we ask whether the
claims are directed to a patent ineligible concept, such as an abstract idea or
law of nature. Alice Corp. v. CLS Bank Int 'l, 573 U.S. 208, 217-18
(2014); Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566
U.S. 66, 75-77 (2012); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d
13 71, 13 7 5 (Fed. Cir. 2015). While method claims are generally eligible
subject matter, claims that are directed only to abstract ideas and/or natural
phenomena are directed to a patent ineligible concept. Ariosa, 788 F .3d at
1376.
Alice Step One
Claim 1 of the instant application is directed to a method of improving
the sensitivity of detecting a target nucleic acid immobilized on a support by
using a plurality of detection probes complementary to the nucleic acid, and
limiting the nucleic acid ( or fragments thereof) to a particular size.
Taking up the first step of the patent-eligibility analysis, we note, "[a]t
some level, 'all inventions ... embody, use, reflect, rest upon, or apply laws
of nature, natural phenomena, or abstract ideas,"' and whether one takes a
macroscopic or microscopic view of a claim may be determinative on the
issue. Alice, 573 U.S. at 217.
Claim 1 is closely analogous to a claim held patent-eligible in Rapid
Litigation Management Ltd. v. CellzDirect, Inc., 827 F.3d 1042 (Fed. Cir.
2016), which involved producing frozen hepatocytes. Id. at 1046.
Just as the claims in CellzDirect were "simply not directed to the ability of
hepatocytes to survive multiple freeze-thaw cycles" (id. at 1048), the instant
claims are simply not directed to a natural phenomenon but rather "a new
9
Appeal2018-005971
Application 14/381,366
and useful laboratory technique" (id.). We agree with Appellants that the
claims are drawn to a "useful laboratory technique, such as a sandwich
hybridization method utilizing 'a plurality of detection probes that hybridize
with different regions of the target nucleic acid"' (Br. 12). We note that
Appellants' position is also consistent with the January 7, 2019
Memorandum, 2019 Revised Patent Subject Matter Eligibility Guidance, 84
Fed. Reg. 50-57 (2019) because these nucleic acid hybridization claims are
not directed to any judicial exception such as mathematical concepts,
organizing human activities or mental processes but are rather drawn to
tangible physical steps that combine target nucleic acids with various nucleic
acid probes to detect the presence of a particular target nucleic acid in a
sample.
The claimed technique "for producing a tangible and useful result,
falls squarely outside those categories of inventions that are 'directed to'
patent-ineligible concepts." CellzDirect, 827 F.3d at 1050. Therefore, these
claims are not directed to a natural phenomenon, and thus, the claims are
patent eligible under Alice step one. We note that "[i]f the claims are not
directed to a patent ineligible concept at step one, we need not address step
two of the inquiry." Vanda Pharms. Inc. v. West-Ward Pharms. Int'! Ltd.,
887 F.3d 1117, 1134 (Fed. Cir. 2018).
We, therefore, conclude that Supreme Court and Federal Circuit
precedent supports the conclusion that the claims on appeal are directed to
patent-eligible subject matter.
10
Appeal2018-005971
Application 14/381,366
New Ground of Rejection
Under the provisions of 37 C.F.R. § 41.50(b ), we enter the following
new ground of rejection. 5
Findings of Fact ("FF'')
1. Collins6 teaches a process of detecting the presence or absence of
nucleic acid in an amount below 100 molecules/ml that includes hybridizing
a target nucleic acid with a capture probe and a plurality of detection probes
(See Collins 2979--2980).
2. Figure IA of Collins is reproduced below:
A. AP label probe-.
capture
extender~
Figure 1, panel A illustrates first generation branched DNA ("bDNA") assay
components, including a target sequence, capture probe, and multiple label
probes attached to the target sequence (Collins 2980).
5 As the Board's function is primarily one of review and not search, we leave
to the Examiner the determination of whether the cited prior art, alone or in
combination with other well-known and easily identified prior art should be
applied to address the remaining dependent claims.
6 Mark L. Collins et al., A branched DNA signal amplification assay for
quantification of nucleic acid targets below 100 molecules/ml., 25 NUCLEIC
ACIDS RESEARCH 2979--84 (1997).
11
Appeal2018-005971
Application 14/381,366
3. Liu7 teaches "[i]n DNA microarray studies, ... the lengths of
nucleic acid molecules are known to affect the rate and efficiency of target-
probe duplex formation ... leading to reduced hybridization efficiencies and
false-negative signals. To address this, solutions focusing on target
fragmentation ... have been proposed and demonstrated" (Liu 80).
4. Liu teaches "[p Joor detection sensitivity resulting from low target
concentrations is usually remedied by PCR amplification prior to
hybridization ... even though these assays can be affected by the biases
associated with enzymatic amplification" (id. at 73).
5. Liu teaches "hybridization efficiency and detection sensitivity can
be greatly improved by shortening ... native rRNA targets to smaller sizes.
Fragmenting native rRNA targets to 20 to 100 nt by using NaOH-and ZnCb-
catalyzed methods not only enhanced hybridization signal intensities by a
factor of 6.1 to 6.2 but also reduced false-negative signals" (id. at 80).
6. Liu teaches "enhanced hybridization efficiencies and reduced false-
negative signals for DNA fragments when the target length was shortened
(Table 1). A reduction in the length of the DNA target from 1,480 bp to
approximately 184 to 193 bp could minimize false-negative signals by a
factor of 2.4 to 5.6" (id. at 81 ).
7. Liu teaches "extremely short fragments could adversely lead to a
slight increase in false-positive signals. Thus, there is a need to compromise
between good hybridization efficiencies and hybridization specificities"
(id.).
7 Wen-Tso Liu et al., Effects of Target Length on the Hybridization
Efficiency and Specificity of rRNA-Based Oligonucleotide Microarrays, 73
APPLIED AND ENVTL. MICROBIOLOGY 73-82 (2007).
12
Appeal2018-005971
Application 14/381,366
8. Small 8 teaches a microarray assay where "hybridization specificity
and signal intensity were enhanced using fragmented RNA" suggesting "that
it is now possible to apply microarray technology to the direct detection of
microorganisms in environmental samples, without using PCR" (Small 4708
( emphasis omitted)).
9. Small teaches:
Notwithstanding the obvious power and utility of PCR,
fundamental uncertainties and errors associated with PCR ...
have significant and mainly negative implications for analysis
of, and interpretation of data from, in situ microbial
communities and environmental samples. . . . The limitations
of PCR ... in an environmental context therefore extend to any
detection method following target amplification, regardless of
the sensitivity, specificity, or multiplexed detection capability
of the sensor element. By extension, the full power and utility
of microarrays to accurately and quantitatively ascribe
phenotype and function to in situ microorganisms will therefore
be realized only by developing techniques for the direct
detection of nucleic acids
(id. at 4713--4714).
Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007). "[W]hen the
question is whether a patent claiming the combination of elements of prior
art is obvious," the answer depends on "whether the improvement is more
8 Jack Small et al., Direct Detection of l 6S rRNA in Soil Extracts by Using
Oligonucleotide Microarrays, 67 APPLIED AND ENVTL. MICROBIOLOGY
4708--4716 (2001).
13
Appeal2018-005971
Application 14/381,366
than the predictable use of prior art elements according to their established
functions." Id. at 417.
"[W]here the general conditions of a claim are disclosed in the prior
art, it is not inventive to discover the optimum or workable ranges by routine
experimentation." In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Analysis
Collins teaches a sandwich hybridization method for detecting a target
nucleic acid that includes the steps: simultaneously hybridizing a target
nucleic acid, a plurality of detection probes that are complementary to
different regions of the target nucleic acid, and a capture probe that is
complementary to a region of the target nucleic acid and is immobilized on a
support; and detecting the presence or absence of the detection probes on the
support (FF 1, 2).
Collins does not teach that the target nucleic acid is fragmented before
hybridization.
Liu teaches improving the detection sensitivity of sandwich
hybridization by using the fragmentation products of target nucleic acids,
including DNA fragments of approximately 184 to 193 bp in length,
overlapping the 100 to 1,500 bases recited in claim 1 (FF 3---6). Small
teaches that a person of ordinary skill would have had reason to use
fragmented nucleic acids in order to enhance hybridization specificity and
signal intensity in order to avoid PCR induced errors (FF 8-9).
We find that it would have been obvious to the person of ordinary
skill in the art at the time the invention was made to use fragment target
DNA as taught by Liu and Small in the sandwich hybridization method of
Collins because Liu teaches "enhanced hybridization efficiencies and
14
Appeal2018-005971
Application 14/381,366
reduced false-negative signals for DNA fragments" relative to unfragmented
target (FF 6) and Small teaches "hybridization specificity and signal
intensity were enhanced using fragmented RNA" (FF 8).
We further find it would have been obvious to a person of ordinary
skill in the art at the time the invention was made to optimize the nucleic
acid target fragment lengths as discussed by Liu and Small because the
nucleic acid length taught by Liu overlaps with the claimed nucleic acid
length, and because "[a] prima facie case of obviousness typically exists
when the ranges of a claimed composition overlap the ranges disclosed in
the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). As
taught by Liu, nucleic acid fragment length is a result effective variable for
using sandwich hybridization to detect a target nucleic acid, where the
fragment should neither be too long nor too short for optimal detection (see
FF 7). "[D]iscovery of an optimum value of a result effective variable in a
known process is ordinarily within the skill of the art." In re Boesch, 617
F.2d 272,276 (CCPA 1980).
SUMMARY
In summary, we summarily affirm the rejection of claim 18 under
35 U.S.C. § 112 (pre-AIA), fourth paragraph as being an improper
dependent claim.
We reverse the rejection of claims 1-3, 5, 7-13, and 16-20 under
35 U.S.C. § 112, first paragraph, omitting essential elements.
We reverse the rejection of claims 1-3, 5, 7-13, and 16-20 under
35 U.S.C. § 112, first paragraph, enablement.
We reverse the rejection of claims 1-3, 5, 7-13, and 16-20 under
15
Appeal2018-005971
Application 14/381,366
35 U.S.C. § 112, first paragraph, written description requirement.
We reverse the rejection of claims 1, 2, and 7 under 35 U.S.C. § 101,
patent-ineligible subject matter.
We enter a new ground of rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Collins, Liu, and Small.
This decision contains a new ground of rejection pursuant to
37 C.F.R. § 4I.50(b). Section 4I.50(b) provides "[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review."
Section 41.50(b) also provides:
When the Board enters such a non-final decision, the
appellant, within two months from the date of the decision,
must exercise one of the following two options with respect to
the new ground of rejection to avoid termination of the appeal
as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence
relating to the claims so rejected, or both, and have the
matter reconsidered by the examiner, in which event the
prosecution will be remanded to the examiner. The new
ground of rejection is binding upon the examiner unless
an amendment or new Evidence not previously of Record
is made which, in the opinion of the examiner,
overcomes the new ground of rejection designated in the
decision. Should the examiner reject the claims,
appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the
proceeding be reheard under§ 41.52 by the Board upon
the same Record. The request for rehearing must address
any new ground of rejection and state with particularity
the points believed to have been misapprehended or
16
Appeal2018-005971
Application 14/381,366
overlooked in entering the new ground of rejection and
also state all other grounds upon which rehearing is
sought.
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure§ 1214.01.
AFFIRMED-IN-PART; 37 C.F.R. § 4I.50(b)
17